The following article features coverage from the American Society of Clinical Oncology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

When it comes to optimal management of patients who had distant recurrence after receiving adjuvant anti–PD-1 monoclonal antibodies for high-risk resected melanoma, some patients may not respond to subsequent anti–PD-1 treatment and should thus change to other types of medications, suggested the results of a study presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.1

In this retrospective study, researchers looked at 136 patients across 16 international melanoma centers whose disease recurred after receiving adjuvant anti-PD-1 monoclonal antibodies for resected stage III/IV cutaneous melanoma. Of these patients, 97 (71%) recurred during adjuvant anti–PD-1 monoclonal antibodies treatment and 40 (29%) recurred after treatment cessation; specifically, 25 patients had to stop receiving treatment early for reasons related to toxicity after about 3 months, 14 stopped after completing 1 year of treatment, and 1 person withdrew consent after 1 month. Median time from therapy onset to recurrence was 4.6 months (IQR 2.7-8.5).

The researchers found that, at initial recurrence, 78 (57%) patients had distant disease — a group that included 22 patients with both distant and locoregional disease. Fifty-nine patients (43%) had locoregional disease only. Of the 59 patients who initially had local recurrence, 22 (37%) eventually went on to develop distant disease. Moreover, 26 (19% of the total number) patients died.

The researchers were able to evaluate responses to systemic therapy for distant recurrence, either first or subsequent, in 92 of 109 patients. Of the 92 patients, 71 initially had disease recurrence while they were receiving adjuvant anti–PD-1 treatment, and 21 had disease recurrence off treatment.


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Among those who had their disease recur during treatment with PD-1 inhibitors, 8 of 33 patients (24%) subsequently responded to ipilimumab-based therapy, either alone or in combination with PD-1 blockade.

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Moreover, 18 of 23 patients (78%) responded to BRAF/MEKi. Only 1 of 9 patients (11%) responded to anti–PD-1 with a novel agent, and no patients responded to anti–PD-1 alone.

“When we look at distant recurrence, the take-home message is that for patients who recur on anti–PD-1, they are resistant to anti–PD-1 and must change treatment,” said lead study author Carina N. Owen, MBBS, of the Melanoma Institute Australia in Sydney.

Among those who recurred off anti–PD-1 treatment, 2 of 5 (40%) subsequently responded to ipilimumab-based therapy, either alone or in combination with anti–PD-1. In addition, 9 of 10 (90%) responded to BRAF/MEK inhibitors. No patients responded to anti–PD-1 with a novel agent. While 2 of 5 patients (40%) responded to anti–PD-1 alone, Dr Owen noted that the number of patients in this particular subgroup was small, and thus more research is needed.

After analyzing data on locoregional recurrence, the researchers concluded that the benefits of further adjuvant therapy after local therapy are unclear and more data are needed.

“Translating these results into clinical practice, combination BRAF/MEK inhibitors are only an appropriate option for patients harboring a BRAF mutation in their tumor (50% of patients in this study). Ipilimumab-based therapy showed promising activity, and can be offered to patients regardless of BRAF mutation status,” commented Carina Owen, MBBS, Melanoma Institute Australia, North Sydney, in an email to Cancer Therapy Advisor. “When evaluating systemic therapy options for BRAF-mutant patients, ORR is not the only factor to consider. Initial response rates to BRAF/MEK inhibitors are high but most patients experience disease progression, as tumors develop resistance. Conversely, ipilimumab-based therapy may offer more durable responses for selected patients despite the observed markedly lower ORR, and should also be considered as a frontline option at recurrence. Clinicians must also factor in the significant toxicity that may be experienced with ipilimumab (irAE G3/4 rate of 40%-50%) when considering appropriate systemic therapy.”

Editor’s Note: This article was updated on June 12, 2019, to include the perspective of the study authors.

Read more of Cancer Therapy Advisor‘s coverage of ASCO’s annual meeting by visiting the conference page.

Reference

Owen CN, Larkin JMG, Shoushtari AN, et al. A multicenter analysis of melanoma recurrence following adjuvant anti-PD-1 therapy.Presented at: 2019 American Society for Clinical Oncology (ASCO) Annual Meeting; May 31-June 4, 2019; Chicago, Illinois. Abstract 9502.